Being the most common and costly intoxication, this activity will review the toxicokinetics of alcohol intoxication. Upon intake, alcohol begins metabolism with extensive first-pass metabolism catalyzed by the enzyme alcohol dehydrogenase (ADH).[25] While all our cells in our body are capable of metabolizing alcohol, most occur in the liver with ADH and CYP2E1 (though CYP450 enzymes do not become active until reaching chronic abuse or ingesting substantial amounts). Ethanol is metabolized initially to acetaldehyde, which gets further metabolized in mitochondria to acetate via acetaldehyde dehydrogenase. While acetate will enter the peripheral circulation for utilization in reactions as the key intermediate acetyl CoA, acetaldehyde forms in addicts, causing injury through activation of immune processes. This reaction finds particular relevance in alcoholic liver disease as ADH and ALDH1 reduce all stores of NAD+ to NADH, affecting NAD+-requiring enzymes like lactate and pyruvate dehydrogenase. The eventual damage is the result of reactive oxygen species (ROS). Typically, glutathione (GSH) stores neutralize ROS, but alcohol depletes GSH stores leaving ROS unchecked. For example, ROS interacts with lipids to undergo lipid peroxidation resulting in malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE), which can go on to form protein adducts.[25] Thus, it becomes clear that alcohol metabolism specifically through the generation of ROS and depletion of reducing agents such as GSH, causes damage to multiple organs in the body such as liver, lung, muscle, and brain.[25]

For reference: The average rate of alcohol metabolism is 7g/hr or roughly one drink/hr.

History and physicals vary vastly depending on the substance ingested, time since ingestion, and route of ingestion. For example, most forms of alcohol intoxication present with slurred speech, ataxia, and impaired judgment. This process, depending on the dose and time-frame of ingestion, can quickly spiral towards CNS depression, coma, and multiorgan failure. This progression applies to ethanol, methanol, isopropanol, and ethylene glycol.

In terms of cocaine and other stimulants, expect an acute patient with anxiety, potential psychosis, and sympathetically-driven vital signs (tachycardia, tachypnea, high blood pressure, etc.). Management begins with decreasing anxiety, stabilizing vitals, and preparing rapid response teams for deteriorating patients.

Also, significant variations are seen based on the stage of addiction and addicted substance. The five stages of addiction are as follows:

1. First use
   1. These are naïve patients in the sense that they have not yet felt the effects of their substance. It could be a new pain medication prescription, or peer-pressure imposed experimentation.
2. Continued use
   1. Individuals begin to return to a medication they no longer “need” but want as well as they notice the post-high sensation does not clear as quickly.
3. Tolerance
   1. Patients in this stage realize they need large doses of the drug to feel prior levels of high.
4. Dependence
   1. Patients begin to show the physical signs of withdrawal from discontinuing use. Worse, patients no longer feel “normal” without their drink or substance.
5. Addiction
   1. These patients can be on one of two sides of the coin. They may be distressed by their continued use but require it despite serious life problems that have resulted, or they may be in denial of the addiction and continue to spiral further into their addiction.

The above descriptions of stages reveal the expected presentation of the addicted patient. History and physical examination will vary based on which the stage of the condition. A first use patient will likely not be in acute distress (barring active trauma/chronic pain) or have physical signs of withdrawal when they present to your clinic or emergency room. The tolerant patient will typically present with a story that necessitates increasing the dose of their medication or unexpected refill. The addicted patient can present in acute withdrawal with symptoms that vary based on the substance. Alcohol withdrawal will present with signs of autonomic dysregulation to the most worrisome, delirium tremens and seizures.

Lab values (blood and urine), imaging, and specific tests vary depending on the root of the addiction. If it is a psychoactive substance, there may be obvious derangements in the comprehensive metabolic panel (CMP)  and complete blood count (CBC) values as well as in the psychoanalysis and behavioral screening. The following is an abbreviated list and summary of common addicted substances and potential evaluation expectations for healthcare professionals:

1. Alcohol –
   1. Ethanol –
      1. CBC – chronic use can cause an elevated (mean corpuscular volume), MCV with megaloblastic anemia from folate deficiency.
      2. CMP – Blood urea nitrogen/creatinine (BUN/Cr) may be above baseline, glucose may be chronically low, and electrolytes may be deranged from dehydration.
         1. Anion gap will be elevated in acute intoxications with a decreased CO2 and decreased bicarbonate to reflect in an actively acidotic state
      3. Methanol will be the same plus developing ophthalmologic issues. Requires regular eye exams while in the emergency room.
      4. Ethylene glycol leads to renal failure necessitating serial BUN/Cr levels and GFR to monitor renal function; oxalic acid kidney stones are common resulting in bloody urine on urinalysis (UA).
   2. Cocaine –
      1. Obvious sympathetic drive expressed through elevated vitals. Patients are typically tachycardic and tachypneic. Patients may present with acute psychosis.
         1. Intoxications may necessitate serial troponins, cardiac stress test, and even a cardiac catheterization. Due to the vasoconstriction of coronary vessels, troponins become regularly elevated.
   3. Opioids – Opposite to stimulants like cocaine, opioids present with parasympathetic symptoms such as bradycardia, hypotension, miosis, hypothermia, and sedation. The worrisome factor is sedation leading to respiratory depression.

Please refer to the clinical pearls section for screening criteria in detail, such as CAGE, AUDIT, and the CIWA criteria.

An evaluation commonly used for addiction screening is the Addiction Severity Index (ASI). The screening evaluates seven domains that include:

1. Medical status
2. Employment and support
3. Drug use
4. Alcohol use
5. Legal status
6. Family/social status
7. Psychiatric status

While the screening lacks in special populations such as the homeless, it has been extensively cross-reviewed to show significant reliability and validity in being the foundation of treatment plans for addicted patients.[26]

Imaging

Although, not routine in clinical practice, imaging may be integrated into the panel of evaluation of addiction. Researchers found that reduction in dopamine2 (DA D2) receptors correlated with decreased activity in anterior cingulate gyrus CG and orbitofrontal cortex OFC In detoxified cocaine abusers.[27]

Liquid Chromatography/Mass Spectrometry and IMS

Some of the substances of use (kratom) and misuse (bath salts) are not identifiable on a regular urine drug screen or blood work. Liquid chromatography/mass spectrometry and ion mobility spectrometry (IMS) methods are used to detect kratom, for example.[21]

Intoxications regularly go hand-in-hand with addictions as they can either be the subject of the addiction or the propelling factor towards behavioral disruptions and suicidal tendencies. For that reason, refer to the following list of intoxications/overdoses and their respective antidotes.

Further management involves monitoring and maintaining patient vital signs. Once again, this is dependent on the stage of presentation of the patient and the subject of the addiction.

While multiple pharmacological treatments are available to the two most common substance addictions – smoking tobacco and alcohol – group meetings and psychological and social support are by far the most effective.

Pharmacologically, alcohol dependence is treatable with disulfiram, naltrexone, and acamprosate.[28] Each has its place in alcohol dependence and addiction. Disulfiram is effective for the patient who recently quit and needs help maintaining abstinence as any consumed alcohol will cause relatively quick hangover-type symptoms meant to deter further drinking. Naltrexone removes the sensation of reward/pleasure with drinking to begin and maintain abstinence, and acamprosate minimizes the initial withdrawal symptoms as you work on becoming abstinent. Acute management of alcohol intoxication during episodes of relapse is treatable with long-acting benzodiazepines such as chlordiazepoxide or diazepam.[28]

For tobacco dependence pharmacologically, there is currently bupropion and varenicline.[29] Off-label uses exist for drugs like clonidine which is an alpha-2 agonist for managing high blood pressure; also, there is nortriptyline, a member of the TCA class of antidepressants. Both of the latter drugs are effective if started before quitting. As for bupropion, the pill is used to cut down your craving for, and thus addiction to, tobacco.[29] Varenicline helps curb the craving for nicotine as well as decreasing withdrawal symptoms.[29] Along with these options, there are various nicotine patches, gums, sprays, and lozenges.

Ultimately, however, these pharmacological interventions must be combined with non-pharmacological methods for optimal efficacy and to limit and prevent the progression of substance use from developing to misuse to dependence. For example, in terms of nicotine dependence, it has been shown that pharmacological treatments employed with physician advice and empathy results in approximately double the rate of long-term abstinence.[29]

Addiction Treatment:

Of interest, more addicts have overcome their addiction in their way vs the amount enrolled in a program (12-step, CBT, etc).[30] For these reasons, consideration is necessary for whether to treat an addict or not. If you do plan to initiate treatment, a joint plan that involves the input of the patient will yield better results than without it. 

In terms of addictions, the differential should include ruling out the root causes of the addiction. Potential root causes are as follows:

Bipolar disorder – more than half of patients with substance abuse disorder have bipolar disorder, and significant mood fluctuations can present in the patient.

Post-traumatic stress disorder (PTSD) – common concurrence amongst alcohol abusers, PTSD should be screened for in all addicts. While the two are separate conditions with separate signs and symptoms, treating the root of the PTSD can mitigate or eliminate the overlying addiction.

Since most cases of intoxication involve episodes of altered mental status, a helpful mnemonic for the emergency room physician is the following:

1. A - alcohol
2. E – encephalopathy (hypertensive, hepatic), electrolytes, endocrine, environmental
3. I – insulin (hypoglycemia, HHNK, DKA)
4. O – opiates, oxygen
5. U – uremia
6. T – trauma, toxins
7. I – infection, increase ICP
8. P – psychosis, poisoning, porphyria
9. S – stroke, shock, seizure

Stages of addiction: refer above to the history and physical discussion to review the stages of addiction.

Stages of recovery/change from addiction include[31]:

1. Precontemplation: the patient still has yet to acknowledge the problem
2. Contemplation: the patient has recognized the problem but not yet dealing with it
3. Preparation: the patient makes a doctor’s appointment to discuss receiving help
4. Action: the patient begins treatment to reach and maintains abstinence
5. Maintenance: the patient has become abstinent and is maintaining through positive coping strategies
   1. Relapse: unfortunately, during the maintenance phase patients may time to time fall into the relapse stage and restart the recovery process

The evidence is quite clear on the long-term effects of drug dependence with those diagnosed dying 22.5 years earlier than those without the diagnosis.[32] This lifespan is related to the toxic effects of substances on multiple systems, including – but not limited to – the cardiac, respiratory, and neurological systems. Also, a five-year study on alcohol and drug rehabilitation treatment found that older adults have favorable long-term outcomes versus young adults; specifically, older adults (especially older women) were found to have 52% 30-day abstinence rates versus a 40% younger adult rate.[32][33] Factors such as social networks and gender play a role alongside age in these numbers.

Based on the current research on addiction, practitioners need to shift the management of patients from an acute paradigm to a chronic disease paradigm.[32] Furthermore, we need to bolster the screening, intervention, and overall management of the condition. Urgency is necessary for this shift as 6.9 million or 2.8% of the US population is currently under threat of the mortality risk associated with illicit drug use.[32] However, before any change gains traction, current research must bolster the evidence of decreased mortality with decreases in prevalence and incidence of addiction.

As of now, there is a clear relationship between the changes in mortality risk with the time at which patients afflicted with addiction enter treatment and the amount of therapy they receive.[32] Their ultimate prognosis depends on these factors.

In terms of chronic alcohol use, Wernicke encephalopathy and Korsakoff syndrome become expected complications. With Wernicke encephalopathy comes the triad of confusion, ophthalmoplegia, and ataxia (though usually, only one is present 20% of the time).[34] On CT and MRI imaging, classic findings include atrophy of the bilateral mammillary bodies and hippocampal areas.[34]

Hepatic steatosis is a common complication of chronic alcohol use that results from cholesterol esters, phospholipids, and triglycerides formed ultimately from alcohol-induced ROS formation altering lipid metabolism.

Chronic heavy alcohol consumption is the most important risk factor when considering chronic pancreatitis. The process begins with acute heavy consumption, which through toxic effects of alcohol metabolism, induce inflammatory and fibrotic changes in the pancreas over time. Specifically, the pancreatic stellate cells become activated, resulting in the expected fibrotic changes.

Cardiomyopathy is another documented complication that is expected as a result of chronic alcohol use resulting from oxidative stress, disruptions in proper calcium handling, and mitochondrial dysfunction.[35]

Cocaine addiction and intoxication lead to myocardial ischemia, psychosis, and fatal arrhythmias that require acute management for mitigation of effects.[36]

From a behavioral perspective, addiction leads to multiple episodes of withdrawal and relapses (the average being 7).

Rehabilitation treatment becomes the cornerstone of managing an addicted patient from sobering up to maintaining their remission. Since the 1960s, various modalities have found public and private aid such as methadone clinics, free outpatient treatment programs, and residential community treatment sites.[37]

Among the most common and effective programs include the 12-step programs; this is category includes AA (Alcoholics Anonymous), Narcotics Anonymous, and Cocaine Anonymous. This is a form of peer support groups that are commonplace in addiction management with the dual benefit of aiding drug addiction reform and co-occurring mental health problems. Some of the positive outcomes of these programs include increased self-confidence, self-efficacy and healthy coping strategies for addicts to maintain their abstinence. Overall, rehabilitation care for addiction management includes failsafes that prevent relapse from happening through pharmacological deterrents and peer-support groups.[38]

Many times psychiatry consults are necessary as the addiction stems from underlying behavioral/psychological issues. However due to the many medical or surgical complications associated with addiction, medical, surgical or trauma consults are also necessary to address impending death due to myocardial infarction, acute kidney failure, rhabdomyolysis encountered with stimulants like cocaine and amphetamine, respiratory arrest and coma by overdose on prescribed or non-prescribed opioids, and motor vehicle accident leading to head injury and traumatic brain injury.

Deterrence is dependent on proper screening criteria for early signs of potential addiction as well as early childhood education. School programs such as DARE represent a positive effort to curb drug use and experimentation before it becomes a problem. However, patient education, while it is most effective prior to the development of health problems, has a place at any stage of addiction. As stated above, patients are more likely to reach and maintain abstinence and institute positive lifestyle changes if physicians and other health care professionals engage in consistent and positive encouragement of the patient. 

Moderate alcohol consumption is defined as 1 drink/day for women and up to 2 drink/day for men. Studies have revealed that this low to moderate alcohol use has been demonstrated to lower the risk of coronary heart disease.

The average rate of alcohol metabolism is approximately 7g/hour which is equal to 1 drink/hour.

Cage criteria for alcoholism screening:

1. Have you ever felt the need to CUT down your drinking?
2. Have people Annoyed you by criticizing your drinking?
3. Have you ever felt guilty drinking?
4. Have you ever felt you needed a drink first thing in the morning (Eye-opener) to steady your nerves or to get rid of a hangover?

Each yes gets a +1, and each no gets a 0 for a total of 4 and a low of 0. However, CAGE falls short in lower severity situations. For these (if provided with ample time for interviewing) refer to AUDIT:

1. How often have you had a drink containing alcohol this past year?
2. How many drinks with alcohol did you have on a typical day you were drinking this past year?
3. How often did you have six or more drinks on one occasion in this past year?

Each question has four potential categories for responses allowing each category a max of 4 and a low of 0. Scores less than 3 are consistent with normal alcohol consumption.

CIWA Criteria:

1. Nausea/Vomiting 0-7
2. Tremor 0-7
3. Paroxysmal sweats 0-7
4. Anxiety 0-7
5. Agitation 0-7
6. Tactile disturbances 0-7
7. Auditory Disturbances 0-7
8. Visual Disturbances 0-7
9. Headache/Fullness in head 0-7
10. Orientation/clouding of sensorium 0-4

Patients less than or equal to a score of 8 do not require medical treatment whereas those above do.

While patients addicted to opioids may develop a tolerance for all other side effects, constipation and miosis remain constant despite the dosage — screen patients with these side effects before signs and symptoms of respiratory depression and other vital sign depressions.

Although variable amongst the states, typical BAC levels that define alcohol intoxication 80 to 100 mg/dL (.08 to 0.1% BAC). For the chronic user, these levels may take increasing times to reach.

Sober time calculator – (BAC (mg/dL) – legal limit) / 20mg/dL/hr = time to sobriety

Avoid bupropion in patients with a current or past history of eating disorders as this lowers the threshold for seizure side-effects.

As discussed above, addiction is a very complex condition with multiple episodes of reaching abstinence and falling into relapse; this is why an interprofessional healthcare team is vital in treatment.

Treatment begins with risk factor identification and diagnosis by the physician but quickly grows to involve interprofessional teams to help the patient maintain their abstinence. With comprehensive questioning, primary care physicians can screen patients using criteria such as the Addiction Severity Index and more to identify at-risk patients. These patients should be followed up closely over the years. At the same time, social and familial support can be called upon to prevent the progression to addiction. 

Once diagnosed, the swift involvement of a psychiatrist and dietician are essential. The psychiatrist can help uncover root causes for the addiction while the dietician can help maintain the patient's overall health. The positive attitude and self-control required to reach and maintain abstinence find pitfalls in poor nutrition and energy reserves. 

During relapses, nurses play pivotal roles. They can help track patient vitals, and proper medication and fluids are provided promptly to manage acute intoxications and aid the patient back towards abstinence.

Pharmacists are also essential members of the interprofessional team dealing with addiction. They may be the first to notice addictive behaviors if the addiction involves prescription drugs. They are also good resources for detoxification, assisting clinicians in treatment and rehab centers, and verifying dosing and checking for drug interactions.

Also discussed above, 12 step programs that involve peer support are integral to the development and maintenance of abstinence. The mentioned players - primary care physician, ER physician, nurses, 12 step programs, dietician, psychiatrists - all have well-researched roles in the success of diagnosing and managing addiction patients. [Level I]

The interprofessional team of clinicians, nursing, specialists, psychological professional, pharmacists, dieticians, and social workers must all coordinate their actions and information to achieve the best possible patient outcomes for addiction disorders. [Level V]